A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease

Yoshihiro Kashiwaya, Christian Bergman, Jong Hwan Lee, Ruiqian Wan, M. Todd King, Mohamed R. Mughal, Eitan Okun, Kieran Clarke, Mark P. Mattson, Richard L. Veech

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) involves progressive accumulation of amyloid β-peptide (Aβ) and neurofibrillary pathologies, and glucose hypometabolism in brain regions critical for memory. The 3xTgAD mouse model was used to test the hypothesis that a ketone ester-based diet can ameliorate AD pathogenesis. Beginning at a presymptomatic age, 2 groups of male 3xTgAD mice were fed a diet containing a physiological enantiomeric precursor of ketone bodies (KET) or an isocaloric carbohydrate diet. The results of behavioral tests performed at 4 and 7 months after diet initiation revealed that KET-fed mice exhibited significantly less anxiety in 2 different tests. 3xTgAD mice on the KET diet also exhibited significant, albeit relatively subtle, improvements in performance on learning and memory tests. Immunohistochemical analyses revealed that KET-fed mice exhibited decreased Aβ deposition in the subiculum, CA1 and CA3 regions of the hippocampus, and the amygdala. KET-fed mice exhibited reduced levels of hyperphosphorylated tau deposition in the same regions of the hippocampus, amygdala, and cortex. Thus, a novel ketone ester can ameliorate proteopathic and behavioral deficits in a mouse AD model.

Original languageEnglish (US)
Pages (from-to)1530-1539
Number of pages10
JournalNeurobiology of Aging
Volume34
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Anti-Anxiety Agents
Ketones
Amyloid
Cognition
Ketone Bodies
Alzheimer Disease
Esters
Pathology
Diet
Hippocampus
Amygdala
Anxiety
Age Groups
Carbohydrates
Learning
Glucose
Brain

Keywords

  • 3xTgAD
  • Amygdala
  • Anxiety
  • Cognitive deficits
  • Energy Metabolism
  • Frontotemporal lobe dementia
  • Hippocampus

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. / Kashiwaya, Yoshihiro; Bergman, Christian; Lee, Jong Hwan; Wan, Ruiqian; King, M. Todd; Mughal, Mohamed R.; Okun, Eitan; Clarke, Kieran; Mattson, Mark P.; Veech, Richard L.

In: Neurobiology of Aging, Vol. 34, No. 6, 06.2013, p. 1530-1539.

Research output: Contribution to journalArticle

Kashiwaya, Y, Bergman, C, Lee, JH, Wan, R, King, MT, Mughal, MR, Okun, E, Clarke, K, Mattson, MP & Veech, RL 2013, 'A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease', Neurobiology of Aging, vol. 34, no. 6, pp. 1530-1539. https://doi.org/10.1016/j.neurobiolaging.2012.11.023
Kashiwaya, Yoshihiro ; Bergman, Christian ; Lee, Jong Hwan ; Wan, Ruiqian ; King, M. Todd ; Mughal, Mohamed R. ; Okun, Eitan ; Clarke, Kieran ; Mattson, Mark P. ; Veech, Richard L. / A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer's disease. In: Neurobiology of Aging. 2013 ; Vol. 34, No. 6. pp. 1530-1539.
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